General Discussion

Congenital hypomyelination neuropathy (CHN) is a neurological disorder present at birth. Major symptoms may include respiratory difficulty, muscle weakness and incoordination, poor muscle tone (neonatal hypotonia), absence of reflexes (areflexia), difficulty in walking (ataxia), and/or impaired abilities to feel or move part of the body.

Signs & Symptoms

Symptoms of congenital hypomyelination neuropathy and the severity of these symptoms vary from patient to patient. Major symptoms can include delayed motor (muscle) development (ability to turn over, stand, crawl, walk, etc.), muscle weakness, poor muscle tone (hypotonia), impaired muscle coordination, absence of reflexes (areflexia), difficulty in walking or crawling, and/or impaired ability to feel or move part of the body (mild distal palsy). In some infants, respiratory problems or difficulty in swallowing may occur. Abnormal microscopic changes in certain nerves such as sural nerves (located in the calf of the leg) can occur.

Causes

The exact cause of congenital hypomyelination neuropathy is not known. The cause of many disorders involving the myelin sheath (the protective sheath surrounding the nerves), such as multiple sclerosis, is unknown. A recurrent loss and repair of myelin causes congenital hypomyelination neuropathy. Scientists do not yet know why the myelin disappears, nor do they know why it grows back.

Researchers have identified changes (mutations) in more than one gene involved in the process of myelin formation. However, it is not well understood at this time how such changes may be related to the development of congenital mypomyelination neuropathy.

Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Human body cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22 and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome and females have two X chromosomes. Each chromosome has a short arm designated “p” and a long arm designated “q”. Chromosomes are further sub-divided into many bands that are numbered.

Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother.

Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%. The risk is the same for males and females.

All individuals carry a few abnormal genes. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder.

Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary for the appearance of the disease. The abnormal gene can be inherited from either parent, or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from affected parent to offspring is 50% for each pregnancy regardless of the sex of the resulting child.

Affected Populations

Congenital hypomyelination neuropathy is a rare disorder present at birth. It affects males and females in equal numbers.

Related Disorders

Symptoms of the following diseases may be similar to those of congenital hypomyelination neuropathy.

Dejerine-Sottas disease is a hereditary neurological disorder which progressively affects muscle function. Peripheral nerves become enlarged and thickened causing an irregular progression of muscle weakness. Pain, weakness, numbness, and a tingling, prickling or burning sensation can occur in the patient’s legs. Other symptoms include loss of heat sensitivity, absence of reflexes and atrophy of leg muscles. The hand and forearm muscles may become weak in later stages. Mild vision difficulties may also occur. (For more information on this disorder, choose “Dejerine-Sottas” as your search term in the Rare Disease Database.)

Guillain-Barre syndrome (acute idiopathic polyneuritis) occurs when the body’s immune system (antibodies, lymphocytes) attacks the nerves, damaging the nerve’s myelin and axon. Nerve signals are delayed and altered, causing weakness and paralysis of the muscles of the legs, arms, and other parts of the body along with abnormal sensations. When muscle nerves are damaged, the patient experiences aching and weak muscles, difficulty getting up from chairs or walking stairs, difficulty lifting objects, shortness of breath, and/or difficulty in swallowing. With proper treatment, most patients with Guillain-Barre syndrome can expect to lead full and active lives. (For more information on this disorder, choose “Guillain” as your search term in the Rare Disease Database.)

Diagnosis

Testing for congenital hypomyelination neuropathy includes measuring the velocity of transmission of electrical impulses produced by the muscles (electromyogram), as well as nerve and/or muscle biopsies.

Standard Therapies

Treatment

Treatment of congenital hypomyelination neuropathy is symptomatic and supportive.

Investigational Therapies

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government website.

For information about clinical trials being conducted at the National Institutes of Health (NIH) in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222

TTY: (866) 411-1010

Email: prpl@cc.nih.gov

For information about clinical trials sponsored by private sources, contact:

NORD's Rare Disease Database provides brief introductions for patients and their families to more than 1,200 rare diseases. This is not a comprehensive database since there are nearly 7,000 diseases considered rare in the U.S. We add new topics as we are able to do so, with the help of rare disease medical experts.

If you are seeking information about a rare disease that is not in this database, we would suggest contacting the Genetic and Rare Diseases Information Center (GARD) at the National Institutes of Health. NIH has the most complete database of rare diseases in the U.S.

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